Since the major natural routes of acquisition of infection are ingestion and transplacental transmission, murine models have been developed to define pathogenesis of and immune response to Toxoplasma infection acquired by ingestion and to determine whether the immune response protects the host and prevents transmission to the fetus in utero when Toxoplasma is subsequently ingested. We are determining whether following ingestion of T. gondii cysts there is intestinal secretory IgA and serum IgA specific for toxoplasma, transformation of lymphocytes to Toxoplasma antigen, homing of lymphocytes to the gastrointestinal tract, and enhanced microbicidal capacity of mononuclear phagocytes. To determine whether immune response prevents transmission of infection with subsequent ingested challenge, nonpregnant and pregnant mice are infected and challenged with intestinally administered cysts and fetal tissue examined for infection. If the immune response to ingested T. gondii prevents transmission when cysts are subsequently administered orally, immunization procedures which stimulate the immune response will be developed and employed to prevent infection. To establish the relevance of these studies to prevention of infection in humans, components of the immune response to infection in humans are being studied. These studies include assays for presence of specific anti-Toxoplasma secretory and serum IgA, and evaluation of microbicidal capacity of mononuclear phagocytes and lymphocyte function.